Radiograph of a rickets sufferer, a complication of both distal and proximal RTA.
Distal renal tubular acidosis (dRTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of acid secretion by the alpha intercalated cells of the cortical collecting duct of the distal nephron. This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to a pH of less than 5.3.
Contents
1Symptoms
2Causes
3Diagnosis
4Treatment
5See also
6References
7External links
Symptoms
Because renal excretion is the primary means of eliminating acid from the body, there is consequently a tendency towards acidemia.
This leads to the clinical features of dRTA:[1]
Normal anion gap metabolic acidosis/acidemia
Hypokalemia
Urinary stone formation (related to alkaline urine, hypercalciuria, and low urinary citrate).[2]
Nephrocalcinosis (deposition of calcium in the substance of the kidney)
Bone demineralisation (causing rickets in children and osteomalacia in adults)
The symptoms and sequelae of dRTA are variable and range from being completely asymptomatic, to loin pain and hematuria from kidney stones, to failure to thrive and severe rickets in childhood forms as well as possible renal failure and even death.
dRTA commonly leads to sodium loss and volume contraction, which causes a compensatory increase in blood levels of aldosterone.[3] Aldosterone causes increased resorption of sodium and loss of potassium in the collecting duct of the kidney, so these increased aldosterone levels cause the hypokalemia which is a common symptom of dRTA.[3]
Causes
Diagram depicting an alpha intercalated cell with the apical proton pump and basolateral band 3 (kAE1)
Autoimmune disease. Classically Sjögren's syndrome, but it is also associated with systemic lupus erythematosus, rheumatoid arthritis and even hypergammaglobulinemia. Hypokalaemia is often severe in these cases.[4]
Hereditary causes include mutations of Band 3[5] the basolateral bicarbonate transporter of the intercalated cell, which may be transmitted in an autosomal dominant fashion in western European cases, or in an autosomal recessive fashion in South East Asian cases. The South East Asian cases are associated with more severe hypokalemia.[6] Other hereditary causes include mutations of subunits of the apical proton pump vH+-ATPase,[7] which are transmitted in an autosomal recessive fashion, and may be associated with sensorineural deafness.[8]
Liver cirrhosis.
Nephrocalcinosis. While it is a consequence of dRTA, it can also be a cause; related to calcium-induced damage of the cortical collecting duct.
Renal transplantation.
Sickle cell anemia.
Toxins, including ifosfamide (more commonly causing pRTA than dRTA),[9] lithium carbonate[10] and amphotericin B.[11]
Chronic urinary tract obstruction.
Toluene causes a non-anion gap metabolic acidosis with hypokalemia and a positive urinary anion gap that looks a lot like distal RTA but there is no hydrogen secretion defect and the acidosis is due to acid production during the metabolism of toluene.[12]
Diagnosis
The pH of patient's blood is highly variable, and acidemia is not necessarily characteristic of sufferers of dRTA at any given time. One may have dRTA caused by alpha intercalated cell failure without necessarily being acidemic; termed incomplete dRTA, which is characterized by an inability to acidify urine, without affecting blood pH or plasma bicarbonate levels.[13] The diagnosis of dRTA can be made by the observation of a urinary pH of greater than 5.3 in the face of a systemic acidemia (usually taken to be a serum bicarbonate of 20 mmol/l or less). In the case of an incomplete dRTA, failure to acidify the urine following an oral acid loading challenge is often used as a test. The test usually performed is the short ammonium chloride test,[14] in which ammonium chloride capsules are used as the acid load. More recently, an alternative test using furosemide and fludrocortisone has been described.[15]
dRTA has been proposed as a possible diagnosis for the unknown malady plaguing Tiny Tim in Charles Dickens' A Christmas Carol.[16][17]
Treatment
This is relatively straightforward. It involves correction of the acidemia with oral sodium bicarbonate, sodium citrate or potassium citrate. This will correct the acidemia and reverse bone demineralisation. Hypokalemia and urinary stone formation and nephrocalcinosis can be treated with potassium citrate tablets which not only replace potassium but also inhibit calcium excretion and thus do not exacerbate stone disease as sodium bicarbonate or citrate may do.[18]
See also
Renal tubular acidosis
Proximal renal tubular acidosis
Ifosfamide
References
^Laing CM, Toye AM, Capasso G, Unwin RJ (2005). "Renal tubular acidosis: developments in our understanding of the molecular basis". Int. J. Biochem. Cell Biol. 37 (6): 1151–61. doi:10.1016/j.biocel.2005.01.002. PMID 15778079.
^Buckalew VM Jr (1989). "Nephrolithiasis in renal tubular acidosis". The Journal of Urology. 141 (3 (part 2)): 731–737. doi:10.1016/S0022-5347(17)40997-9. PMID 2645431.
^ abWein, Alan, J (2011). Campbell-walsh Urology Expert Consult(PDF) (10th ed.). Philadelphia, PA: W B Saunders Co. p. 1045. ISBN 978-1-4160-6911-9.
^Wrong OM, Feest TG, MacIver AG (1993). "Immune-related potassium-losing interstitial nephritis: a comparison with distal renal tubular acidosis". Q. J. Med. 86 (8): 513–34. doi:10.1093/qjmed/86.8.513. PMID 8210309.
^Bruce LJ, Cope DL, Jones GK, et al. (1997). "Familial distal renal tubular acidosis is associated with mutations in the red cell anion exchanger (Band 3, AE1) gene". J. Clin. Invest. 100 (7): 1693–707. doi:10.1172/JCI119694. PMC 508352. PMID 9312167.
^Bruce LJ, Wrong O, Toye AM, et al. (2000). "Band 3 mutations, renal tubular acidosis and South-East Asian ovalocytosis in Malaysia and Papua New Guinea: loss of up to 95% band 3 transport in red cells". Biochem. J. 350 Pt 1 (Pt 1): 41–51. doi:10.1042/0264-6021:3500041. PMC 1221222. PMID 10926824.
^Karet FE, Finberg KE, Nelson RD, et al. (1999). "Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness". Nat. Genet. 21 (1): 84–90. doi:10.1038/5022. PMID 9916796.
^Skinner R, Pearson AD, English MW, et al. (1996). "Risk factors for ifosfamide nephrotoxicity in children". Lancet. 348 (9027): 578–80. doi:10.1016/S0140-6736(96)03480-0. PMID 8774570.
^Boton R, Gaviria M, Batlle DC (1987). "Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy". Am. J. Kidney Dis. 10 (5): 329–45. doi:10.1016/s0272-6386(87)80098-7. PMID 3314489.
^McCurdy DK, Frederic M, Elkinton JR (1968). "Renal tubular acidosis due to amphotericin B". N. Engl. J. Med. 278 (3): 124–30. doi:10.1056/NEJM196801182780302. PMID 5634966.
^Carlisle, E. J.; Donnelly, S. M.; Vasuvattakul, S.; Kamel, K. S.; Tobe, S.; Halperin, M. L. (February 1991). "Glue-sniffing and distal renal tubular acidosis: sticking to the facts". Journal of the American Society of Nephrology. 1 (8): 1019–1027. ISSN 1046-6673. PMID 1912400.
^Batlle, D.; Haque, S. K. (2012). "Genetic causes and mechanisms of distal renal tubular acidosis". Nephrology Dialysis Transplantation. 27 (10): 3691–3704. doi:10.1093/ndt/gfs442. PMID 23114896.
^Wrong, O; Davies HEF (1959). "The Excretion of Acid in Renal Disease". QJM. 28 (110): 259–313. PMID 13658353.
^Walsh SB, Shirley DG, Wrong OM, Unwin RJ (2007). "Urinary acidification assessed by simultaneous furosemide and fludrocortisone treatment: an alternative to ammonium chloride". Kidney Int. 71 (12): 1310–6. doi:10.1038/sj.ki.5002220. PMID 17410104.
^Lewis D (1992). "What was wrong with Tiny Tim?". Am J Dis Child. 146 (12): 1403–7. doi:10.1001/archpedi.1992.02160240013002. PMID 1340779.
^Morris RC, Sebastian A (2002). "Alkali therapy in renal tubular acidosis: who needs it?" (PDF). J. Am. Soc. Nephrol. 13 (8): 2186–8. doi:10.1097/01.ASN.0000027973.07189.00. PMID 12138154.
External links
Classification
D
OMIM: 179800
MeSH: D000141
External resources
MedlinePlus: 000493
v
t
e
Diseases of the urinary system (N00–N39, 580–599)
Kidney disease
Glomerules
Primarily nephrotic
Non-proliferative
Minimal change
Focal segmental
Membranous
Proliferative
Mesangial proliferative
Endocapillary proliferative
Membranoproliferative/mesangiocapillary
By condition
Diabetic
Amyloidosis
Primarily nephritic, RPG
Type I RPG/Type II hypersensitivity
Goodpasture's syndrome
Type II RPG/Type III hypersensitivity
Post-streptococcal
Lupus
DPGN
IgA/Berger's
Type III RPG/Pauci-immune
Granulomatosis with polyangiitis
Microscopic polyangiitis
Eosinophilic granulomatosis with polyangiitis
General
glomerulonephritis
glomerulonephrosis
Tubules
Renal tubular acidosis
proximal
distal
Acute tubular necrosis
Genetic
Fanconi syndrome
Bartter syndrome
Gitelman syndrome
Liddle's syndrome
Interstitium
Interstitial nephritis
Pyelonephritis
Balkan endemic nephropathy
General
General syndromes
Nephritis
Nephrosis
Renal failure
Acute renal failure
Chronic kidney disease
Uremic pericarditis
Uremia
Diabetes insipidus
Nephrogenic
Renal papilla
Renal papillary necrosis
Major calyx/pelvis
Hydronephrosis
Pyonephrosis
Reflux nephropathy
Vascular
Renal artery stenosis
Renal ischemia
Hypertensive nephropathy
Renovascular hypertension
Renal cortical necrosis
Other
Analgesic nephropathy
Renal osteodystrophy
Nephroptosis
Abderhalden–Kaufmann–Lignac syndrome
Urinary tract
Ureter
Ureteritis
Ureterocele
Megaureter
Bladder
Cystitis
Interstitial cystitis
Hunner's ulcer
Trigonitis
Hemorrhagic cystitis
Neurogenic bladder dysfunction
Bladder sphincter dyssynergia
Vesicointestinal fistula
Vesicoureteral reflux
Urethra
Urethritis
Non-gonococcal urethritis
Urethral syndrome
Urethral stricture/Meatal stenosis
Urethral caruncle
Any/all
Obstructive uropathy
Urinary tract infection
Retroperitoneal fibrosis
Urolithiasis
Bladder stone
Kidney stone
Renal colic
Malakoplakia
Urinary incontinence
Stress
Urge
Overflow
v
t
e
Electrolyte imbalance and acid–base imbalance (E86–E87, 276)
Volume status
Volume contraction (dehydration/hypovolemia)
Hypervolemia
Electrolyte
Sodium
High
Hypernatremia
Salt poisoning
Low
Hypotonic
Isotonic
Potassium
High
Low
Chloride
High
Low
Calcium
High
Low
Acid–base
Acidosis
Metabolic: High anion gap
Ketoacidosis
Diabetic ketoacidosis
Alcoholic ketoacidosis
Lactic
Normal anion gap
Hyperchloremic
Renal tubular
Respiratory
Alkalosis
Metabolic
Contraction alkalosis
Respiratory
Both
Mixed disorder of acid-base balance
UpToDate Contents
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Distal renal tubular acidosis is a disease that occurs when the kidneys do not properly remove acids from the blood into the urine. As a result, too much acid remains in the blood (called acidosis).
dRTA (distal Renal Tubular Acidosis) - a resource center for patients and their families. dRTA is a rare type of kidney disease that can have a have major impact on a person’s health throughout their life. National Kidney Foundation ...
Distal renal tubular acidosis (dRTA) is a disorder of impaired net acid secretion by the distal tubule characterized by hyperchloremic metabolic acidosis. The classic form is often associated with hypokalemia whereas ...